Brain and Immune Inflammation: Rising Out of Chronic Physical and Mental Stresses

Long-Term Low Motivation, Brain Fog and Illness Recovery: Is It Within Motivational Control?

Why is it that we often feel listless and/or agitated while we are recovering from an illness, or even long after? There is new information that low-grade chronic inflammation interferes with the dopaminergic signaling system in the brain that motivates us to do things. Dopamine is a neurotransmitter with influences upon mood, motivation, and motor coordination. And, as many of us understand, where there is depression or low motivation, there is frequently agitation. The two forces counter one another in an odd teeter-totter like fashion, trying to both stimulate and calm the mind and body to achieve balance.

The underlying hypothesis of this research is that the body needs more energy to overcome an infectious or pathogenic onslaught, for instance, both of which are associated with acute and/or low-grade inflammatory processes. All body functions require energy, and all are drawing on the same pool of available adenosine triphosphate (ATP) which is the energy source of every cell in the body. When extra demands are placed on this pool without extra filling of the pool, something has to “give”. To ensure that energy is available to the immune system, the brain uses an adaptive technique to reduce the natural drive to perform other tasks which could potentially drain away the energy needed for healing. This produces a recalibration of the specialized reward neurons in the center of the brain which stimulates motivation. The end result is that ordinary pleasurable tasks no longer produce a sense of reward. This provides us with an understanding that this response is likely not within conscious control of the affected person.

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The Stigma and the Possible Antithesis

Countless people who have experienced significant immune events find themselves in very long-term periods of low energy, low motivation, and poor cognitive function. It is frequently the case that they are then labeled as mentally ill with depression, agitation, bi-polar disorder, etc. They are judged for not responding, not healing, and not moving forward. But is this really the problem? I do not believe it is.

Inflammatory cytokines that are naturally produced in an immune crisis have been shown to have a direct effect on mesolimbic dopamine (DA). This effect is a reduced willingness to expend effort for reward. the metabolic demands of chronic low-grade inflammation induce a reduction of striatal DA that in turn leads to a reduced perceived ability (can’t) versus preference (won’t) for reward.

Certain pathogenic and/or injurious episodes, in particular, will cause more long-term chronic responses than others, such as mold poisoning and head injury. Both of these insults can lead to increased vulnerability to other infections and failure of the immune system to modulate itself. Balances of the TH1 and TH2 cells in the immune system are critical, and in cases of chronic inflammation and cytokine storms, are often disturbed. This can cause a failure of autophagy in the inflamed areas of the brain, which may result in symptoms of depression and/or agitation. How often is this then diagnosed as “mental illness” when it may very well be a manifestation of poor immune and cellular recovery? Let’s take a deeper look at autophagy….

Autophagy and the Feedback Loop with Immune Success

So, what exactly is autophagy? It is the body's way of cleaning out damaged cells. “Auto” means self and “phagy” means eat. So the literal meaning of autophagy is “self-eating.” Autophagy is required in order for the body to regenerate healthy cells, including white blood cells. In their mutual feedback loop, autophagy cannot be completed without adequate white blood cells.

The first step of autophagy is the formation of the autophagosome, the lipid sphere the cell builds around the damaged organelle or cellular debris. The autophagosome can then be merged with a lysosome, which produces enzymes that degrade the damaged organelle. The degraded organelle is made into building blocks to build new organelles. Formation of the autophagosome depends on interferon gamma (IFNɣ) and is inhibited by interleukin-4 (IL-4). Imbalances in the TH1 and TH2 cells in the immune system activate the IL-4 pathway. This inhibits the cooperation of autophagy and cell renewal. And, autophagy is essential for the self-repair of brain cells.

Autophagy is associated with health and longevity, and is critical for protecting haematopoietic stem cells from metabolic stress. Loss of autophagy in haematopoietic stem cells causes accumulation of mitochondria and an activated metabolic state, which then drive accelerated myeloid cell differentiation mainly through epigenetic deregulations. Mitochondrial dynamics maintain normal mitochondrial function by degrading damaged mitochondria and generating newborn mitochondria. The accumulation of damaged mitochondria influences the intracellular environment by promoting mitochondrial dysfunction, and thus initiating a vicious cycle. Haematopoietic stem-cell self-renewal activity and regenerative potential are also then impaired.

So, the interplay between the immune system, the brain and dopaminergic system, and autophagy highlights the ongoing struggle of the body to regain homeostasis in the presence of chronic inflammation.

The Puzzle Pieces of Healing with Chronic Immune and Brain Inflammation

In all situations of failed homeostasis, we must come to the baseline requirement to stabilize and/or increase ATP, the universal energy donor in every cell of the body. Mitochondrial respiration is the set of metabolic reactions and processes requiring oxygen that takes place in mitochondria to convert the energy stored in macronutrients to ATP. The most effective way to achieve optimization of ATP is through optimization of the Krebs cycle. ATP essentially binds to proteins in the mitochondria and provides heat to unfold them and generate energy. Additionally, self-generated water is provided to cells through these optimized metabolic processes, stabilizing hydration and electrolytes. In my practice, this begins with assessment of your metabolic nutritional processing and needs. Metabolic Typing ® has been with us for a very long time, and is a proven method to optimize biochemical individuality in one’s nutrition. There are no one-size-fits-all nutritional approaches that work, but only biochemical individuality. Through the use of this nutritional format, we are also addressing all homeostatic mechanisms, such as blood sugar regulation, pH balance, electrolyte balance and blood pressure - all critical metabolic mechanism necessary for health and cooperation of body systems.

Following this stabilization, we must carefully investigate and assess your individual immune and toxic risks. To do this, a careful history is taken and pieced together with symptoms and deficits. Testing is chosen to get specific information on risks and needs for therapeutic application. Individualized protocols are then developed and implemented to restore balance and modulation in the body. In cases of poor brain function and motivation, outside therapies to address limbic system dysfunction and neuroplasticity may be recommended with the potential for exponentially improved healing.
We must always view the body in systems vs. in compartments, and this is the True Nature commitment.